Hepatic encephalopathy (HE) is a complex medical condition involving an acute degeneration in mental status leading to coma and death if untreated. Cerebral edema and elevated intracranial pressure is a consistent finding in HE. Morphologically cerebral astroglial cells are swollen with little change in extracellular volume, characteristics of cytotoxic cerebral edema. Considerable alterations occur in blood chemistry during HE including increased concentrations of ammonia, fatty acids and a variety of aromatic amino acids. Elevated concentrations of these compounds in the serum may initiate a variety of metabolic changes in the brain during HE including alterations in blood flow, energy metabolism, and blood-brain barrier transport. Each of these metabolic perturbations may contribute to the development of cerebral edema. This research project will investigate the role that amino acid transport plays in the development of regional brain edema and in the regulation of brain water content during HE. Based on preliminary studies performed by the Principal Investigator and Foreign Collaborator, we shall measure transport of amino acids which may serve as osmoeffectors in the brain. Transport will be measured in situ across the blood-brain barrier and in preparations of brain tissue slices and capillaries. We also shall determine whether this transport is altered in encephalopathic animals during volume regulation imposed by alterations in perfusing medium osmolality. These experiments will contribute to the goals of the parent grant by exploring the mechanisms of brain edema development in HE and the role of amino acid transport in brain water and cellular volume regulation. Future studies can use these results to determine whether serum factor(s) present in HE disposes the brain to develop edema by altering transport.